We propose to characterization a line of knockout mice that are deficient in the enzyme cholesterol sulfotransferase 2B (SULT2B). This enzyme synthesizes cholesterol sulfate, which is hypothesized to be an end-product of cholesterol turnover, as essential lipid of the skin barrier, and a regulator of keratinocyte differentiation. Standard methods of gene targeting will be employed to generate Sult2b-/- mice, which will be characterized with respect to cholesterol metabolism and skin biology. These studies will provide new insight into the role of lipids in the skin, and perhaps into disorders of this tissue.